CHEM 301 Biochemistry Lecture Notes, 2024-2025 PDF
Document Details
Uploaded by Deleted User
2025
BSMLS-2F
Milliem Reyes
Tags
Summary
These are lecture notes for a Biochemistry course (CHEM 301), likely from the academic year 2024-2025. The notes cover glycogen formation and breakdown, focusing on glycogen and its related processes like glycogenesis and glycogenolysis, and related details on isomerization.
Full Transcript
CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 ○ Insulinstimulatesglycogen synthase OTHER METABOL...
CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 ○ Insulinstimulatesglycogen synthase OTHER METABOLIC PATHWAYS andglucokinase Main enzyme when you are fed GLYCOGEN FORMATION AND BREAKDOWN Released pag kakakain lang; will help glucose enter the cell to either undergo glycolysis or for storage if GLYCOGEN there is excess ○ Glucagonandepinephrineinhibits glycogen synthase Glucagon is the main starving/fasting hormonethat inhibits glycogen synthase therefore inhibiting glycogenesis When we are fasting/starving, we don't want to store excess glucose, we would want to use it right away M ade up of alpha-d glucose units Storage formof Carbohydrates in animals Primarily found in muscle and liver tissues GLYCOGENESIS 1 | ISOMERIZATION A ny glucose that does not undergo glycolysis (excess glucose) Formation of glycogenfrom glucose Location:Cytosol of liver(&muscle) ○ Muscle - storage of glycogen Influenced byhormones Enzyme:Phosphoglucomutase NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |22 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 ○ M utase - transfer phosphate group from one carbon to another Shifts phosphatesbetween carbons G6P 🠆 G1P From glucose (in glycolysis), then hexokinase will act on to become G6P. As G6P can no longer exit the cell, the excesses will now go to glycogenesis to be converted to glycogen 2 | ACTIVATION A ttachment or transfer of the UDP glucose to the growing chain of glycogen Enzyme:Glycogen synthase Stimulatedbyinsulin RATE-LIMITING STEP! Formsα(1🠆4) bonds Straight chain is α(1🠆4), when branched, will be α(1🠆6) 4 | BRANCHING Adding of UTP using an enzyme ○ Enzyme:UDP-glucose pyrophosphorylase Activator:Uridine diphosphate(U DP) UMP attaches to G1P From being UTP, one of its phosphate plus the uridine will attach to glucose-1-phosphate to produce UDP E nzyme:Amylo α(1🠆4) 🠆 α(1🠆6) glucose transglucosidase ○ Naa na tay 1 phosphate from G1P, and Formation ofnew α(1🠆6) bonds the other one that is needed para maka ○ By transferring5-8 glucosyl residues form ug UDP, kay kuhaon nato from UTP. from the core chain Without UDP(energy needed for it to attach),glucose cannot attachto the core GLYCOGENOLYSIS chain of glycogen E xactopposite of Glycogenesis Important for glucose to be allowed to Lysis =cutting of glycogen attach to the chain Breakdown of stored glycogen to form 3 | TRANSFER glucose in thefasting state Location:cytosol of liver(& muscle) Kase glycolysis happens in the cytosol so it makes sense na both glycogen synthesis and glycogen breakdown is in the cytosol as well. Substrate:GLYCOGEN Products: NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |23 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 G ○ LUCOSE= Liver (‘Lover’) C oenzyme:Vitamin B6(in the form of ○ G6P= Muscle (‘Madamot’) Pyridoxal phosphate) ○ This is the reason why the liver can Sequential cleavage ofα(1🠆4) bonds provide glucose for other organs. They Phosphorylation of Glucose can release the glucose out of the cell ○ Forms G1P and share it with others. But because in ○ Continues untillimit dextrin (4 glucosyl the muscle, hanggang G6P lang, it’s units) trapped inside the muscle cell and Pag apat na ang natira na glucosyl therefore it cannot be shared. Whatever units, hindi na kaya ni glycogen glycogen is in the muscle is only for phosphorylase. itself. What will we do with that limit Influenced by hormones (opposite of dextrin? We will get to that later. glycogenesis) Focus muna sa G1P that formed. ○ Insulin Inhibitsglycogen synthase * | ISOMERIZATION & 1 Insulin is for the fed state, wala DEPHOSPHORYLATION tayong glucose na excess kaya hindi tayo gumagawa ng glycogen. ○ Glucagon and Epinephrine Stimulatesglycogen phosphorylase Enzyme:Phosphoglucomutase Isomerization ofG1P🠆G6P 1 | PHOSPHORYLATION ○ The 2 products in glycogenolysis are Glucose and G6P. So, G1P is not enough. ○ With the enzyme Phosphoglucomutase, we can just use that to get from G1P to get to G6P as it is reversible. Therefore, in themuscle, G6P is enough. But in theliver, we have to get back to glucose. ○ Enzyme:Glucose-6-phosphatase Phosphate from carbon 6 of G6P will be removed to get to glucose ○ Happens only in theliverand alittle bit Enzyme:Glycogen Phosphorylase in the kidney. NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |24 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 Q uestion: Does the muscle have Cleavageof α(1→6) bonds glucose-6-phosphatase? Yields free glucose NO. The muscle does not have Breaking an α(1→6) bond, and yielding free glucose-6-phosphatase kaya hanggang glucose. G6P lang siya. Inthesamewayasyoutookapartthe5-8to branch it—you took apart the branchbefore 2 | TRANSFER getting the glucose residues. The last debranching is just for theverylast glucosyl unit, right before dumating ka sa core chain. E nzyme:Glucan transferase Cleavage of α(1→4) bonds 3glucosylunitoflimitdextranmovestocore T hisisacomparisonofwhathappensinthe chain glycogenolysis in the liver and the muscle. Now that the straight chain is cut from the Liver = complete because of core chain, what will we do to the limit glucose-6-phosphatase, yielding a free dextrin? We will TRANSFER. glucoseintheend.Thatglucosecanescape Like how we transferred 5-8 glucosyl into thebloodstreamandbesharedtoother residues to create a new branch, we will organs transfer3glucosylunitsfromthelimitdextrin Muscle: no glucose-6-phosphatase. So back to the core chain. glucose-6-phosphate will ALWAYS push You will cleave the α(1→4) bonds between forward into glycolysis (since the last glucosyl unitandthelastthree.And glucose-6-phosphate can no longer exit the those last three will be brought back to the cell) core chain. Then, we can just continue cutting it (the α(1→4)bondthenanotherα(1→4)bond).But GLUCONEOGENESIS there is still a remaining α(1→6) bond [next step]. 3 | DEBRANCHING Enzyme:Amylo α(1→6) glucosidase NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |25 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 mass is already used up. S ummary of what happens with gluconeogenesis. You can go from lactate, going back to pyruvate (anaerobic). It is a reversible reaction—go back to pyruvate, go to gluconeogenesis, and regenerate G eneratenewglucose.Buttheglucosewill glucose. be generated from noncarbohydrate sources LIPID METABOLISM Productionofglucosefromnoncarbohydrate sources: ○ Lactate ○ Allaminoacids(exceptLandK)[leucine and lysine] ○ Glycerol from fats Location:Liver (90%) Employed when glycogen stores are depleted (12-18h) [12-18 hours after fasting—extent that glycogen is used up] W here does digestion of lipids start? ○ This is the concept of intermittent STOMACH fasting—break down fats during ○ Theonlythingthatstartsdigestioninthe intermittent fasting because you are mouth are carbohydrates (salivary forcing your body to go into amylase). The rest will start in the gluconeogenesis. stomach. ○ Because the order in which your body In the stomach, you’ll have a CHURNING uses up energy: it will first use glucose ACTION, which will put your lipids into fat (thatyoufedit,directly?).Thenifyoudo droplets calledCHYME. nothaveexcessglucose,youwilluseup ○ Gastric lipases will be able to your glycogen stores. After glycogen, it hydrolyze about 10% of TAGs. Those will use up your fats (like glycerol), and triacylglycerols will move towards the then it will use the proteins (amino acids). small intestine. ○ This is the reason also why peoplewho Once in the small intestine, itwillstimulate are in the hospital for a long amount of the release of cholecystokinin (CCK) from time (they are sick so the bodyisdoing the enteroendocrine cells. That CCK will extra work—it needs more energy). activate or stimulate the movement and Eventually, if they stay long there, they contraction of the gallbladder and the grow very thin, because they’re muscle NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |26 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 ommon bile duct so that… c A byproductformedfrombeta-oxidationof ○ Thegallbladderwillreleasesomeofthe fatty acidsduring fasting stored bile DuringFASTING ○ In the common bile duct, theenzymes ○ TCA cycle slows down because of the that come from the pancreas will be lack of glucose provision pushed out. Build up of Acetyl CoA ○ Pancreatic lipases (come from the Unused acetyl CoA from pancreas) previous cycles build up and Once those get to the small intestine, they eventuallyform3typesofketone will now help further metabolize or bodies breakdown the fast. For the most part, ○ 3 Types of Ketone Bodies: almost all digestion will be finished here in 1. Acetoacetate the small intestine. 2. β -Hydroxybutyrate ○ The small intestine will also be where 3. Acetone thoseTAGs will be absorbed. Formed throughketogenesis Those TAGs are absorbed first by the lymphatic system using LACTEALS KETOGENESIS (specialized vessels of thelymphaticsystem Synthesis of ketone bodies from acetyl CoA in the small intestine). ○ Process that creates the keto bodies ○ The lacteals will absorb ortakeinfirst Location:Liver mitochondria the lipids, and then transport it tothe blood(since may katabi na capillaries). ○ Then it will be transported to the bloodstream, so that later on,theycan becomeyourchylomicrons,apoB,etc. (they will be repackaged) Oncetheyareinyourbloodstream,theycan undergo beta oxidation to form energy (not discuss much further) ○ One of the byproducts of the beta oxidationoffattyacidsduringfastingare KETONE BODIES. (This will not be ACETOACETATE happening if there is enough glucose in the body). First ketonebody produced is acetoacetate ○ Process:Condensationof2acetylCoA molecules +removal of Coenzyme A KETONE BODIES β - HYDROXYBUTYRATE P roduced in mitochondria of hepatocyte (liver cell) ○ Process:Reductionof acetoacetate NADH oxidizes to donate its Hydrogen ion to acetoacetate ACETONE ○ Produced in the bloodstream and NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |27 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 ainly excreted by exhalation m technically they enter a state ○ Process: decarboxylation of similar tostarvation acetoacetate Thus an accumulation of ketone Someacetoacetategoesdirectlyinto bodies and a state of ketosis the bloodstream and is Lowering of blood pH occurs → decarboxylated blood becomes acidichencethe CO2 is removed to form acetone term“Diabeticketoacidosis”for ○ Odor:Sharp, strong, and fruity diabetics. Because it isVOLATILE ○ Diets high in fat and low in carbs DissolvesinthebloodandCO2 is Diets high in fat and low in carried within the blood which carbohydrates, such as the Keto decreases the pH of our blood Diet, force the body into a state of Since volatile, it is released as a ketosis. By abstaining from carbs gas and can be smelled on the and consuming fats, the body skips breath of people with a lot of the use of glucose and glycogen, ketone bodies (Ketosis) insteadrelyingdirectlyonfattyacids for energy. KETOSIS Not recommended for everyone especially if diabetic or pre-diabetic ○ Alcoholism ○ Starvation (NOT fasting) A person fasting may enter ketogenesis but not necessarily a state ofketosis(notinexcess;pHis not super low) Starvation→severaldaysoraweek not eating so a large number of Accumulation of ketone bodies ketone bodies accumulate ○ Lowers blood pH You canfastwhilenotbeingina Due to: severe state of ketosis acetoacetate and beta-hydroxybutyrate RECALL → Carboxylic acids What are the 3 ketone bodies? release of CO2 to create acetone ○ Acetoacetate, β-Hydroxybutyrate, Acetone ○ Normal blood pH for Homeostasis: 7.4 Which one is volatile? (about 7.35 to 7.45) ○ Acetone Change in blood pH cancausevast Breath of people with ketosis smell effects such as rapid breathing to like acetone quicklyrelease CO2 from the body What is ketosis? Occurs in ○ Severe diabetes DEGRADATION OF PROTEINS AND AA’S Lack of insulin (not enough or no longer detected) If the body does not produce or detect insulin, glucose cannot enter the body cell and NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |28 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 individual amino acids. Those individual amino acids are transportedintothecellsviaspecific transporters One transporter per amino acid. Those amino acids can bereused So kunwari I have glutamine tas need ko ng glutamine to form a certain new protein sogagamitin ko siya. But for the rest what will happen? ○ Yung mga excess na hindi nagamit for process in the body. We call that entire F orproteins, similarly,the digestion proper processproteinturnover,andthereare will start in the stomach. 2 stages. Nothing happens in the mouth other 2 stages: than the mechanical chewing. ○ Removal of amino group Digestion start:Stomach ○ Degradation of carbon skeleton Amino acids cannot be stored and thus STOMACH are catabolizedforenergyproductioninthe liver Hydrochloric acid, which is very important. ○ Transamination ○ It's at a pH of about1.5 to 2to ○ Oxidative Deamination breakdown proteins ○ Urea cycle Pepsinwill also help hydrolyze peptide bonds. OTHER METABOLIC PATHWAY By the end, you will getlarge polypeptides. Y ou cannot store amino acids.So, how Once these polypeptides get to the are you going to eliminate it? small intestine, it will nowstimulate the ○ Transamination release of certain zymogens or ○ Oxidative Deamination inactivate enzymesfrom thepancreas. ○ Urea Cycle While they’re in the pancreas , Thecarbon portionof each amino acid is they’re inactivated. But once these easy to reuse. It can be used for the creation zymogens get to the small intestine, of new fatty acid, gluconeogenesis, citric which has a more alkaline pH, they acid cycle or ketone bodies. become activated. Thenitrogen portionis the one that is hard Trypsin, in the small intestine, but is necessary to eliminate the zymogen form or the inactive ○ Eliminate it by urea form is still trypsinogen. ○ Use nitrogen for anything that requires Trypsinogenis the term used if nitrogen in the body. it’s still in thepancreas. The moment Trypsinogen meets TRANSAMINATION the alkaline pH of the small Intestine, it will become Trypsin. E limination of nitrogen Like fatty acids, digestion of protein Transferring of amino gluconate ends and they will become NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |29 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 W e get alpha amino acid and alpha keto acid to create new keto acid and new amino W hy do ammonium ions need to be acid released? Kasi super toxic sa body if mag ○ Example from Krebs cycle is Alpha keep sa body. ketoglutarate How are we going to eliminate it? In the form In transamination of amino acids, we ofurea. usealpha ketoglutaratelikealanine Production of urea from the waste of the as itsamino groupto exchange with body the keto group via alanine ○ Waste products areammonium ionand transaminase tocreate pyruvate carbon dioxide and glutamate. Carbon dioxide is the waste product Which of the two products can be of respiration. seen in any amino acid?Glutamate. Some of the amino acids we will be needing Always an amino group plus alpha are arginine, ornithine and citrulline. ketoglutarate skeleton. ○ From that ammonium ion and CO2 will We used alanine as an example create carbamoylphosphate. Then with because alanine is free born in the ornithine, citrulline comes in aspartate to muscle and pyruvate siya kaagad produce argininosuccinate. Lalabas ang meaning, it can easily enter the krebs arphastate na modified aspartate as cycle. fumarate and then will form arginine. Together with the interaction of water OXIDATIVE DEAMINATION molecules, it will become urea. Urea is kind of similar to krebs cycle R emoval of Amine Group Reversing the kreb's cycle to get rid of urea You convert an amino acid (in this case ○ The fumarate will go back to kreb’s glutamate) to a keto acid. Going back to cycle alpha ketoglutarate and releasing For other amino acids we break down, they ammonium ion (NH4+) can come back into our krebs cycle or ○ Will use glutamate as an example as it glycolysis through these ones. can be obtained in any amino acid and it ○ Example: Arginine and aspartate acn has the amino group come back to the TCA via oxaloacetate. Happens in the mitochondria of the liver. ○ Isoleucine, methionine, and valine can Using glutamate dehydrogenase that will be come back to succinyl coA received by either NADP or NAD as ○ Isoleucine, leucine and tryptophan can coEnzyme. come back through acetyl coA; etc ○ Glutamate dehydrogenase is special in that way kasi “hindi mapili”. As long as Be familiar with the photo below. there is a niacin group it can become a coenzyme. The amino group will be released. Placing back oxygen from the water in the body to HEMOGLOBIN CATABOLISM become alpha ketoglutarate. The generated alpha ketoglutarate will be used again for H emoglobin is found in the RBC the Krebs cycle or another transamination Lifespan is 80 to 120 days after that, the process. RBC will deteriorate. ○ Once damaged, your macrophages or UREA CYCLE phagocytic cells will eat the damaged NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |30 CHEM 301-LEC: BIOCHEMISTRY LECTURE A.Y. 2024-2025 | 2ND YR 1ST SEM | FINALS BSMLS-2F | Doc. Milliem ReyesL1|L2|L3 BC and degrade it, releasing the R Paper size: Letter hemoglobin. The GLOBIN PART = PROTEIN PART ICTURES P The HEME PART = BILIRUBIN Centered ○ The bilirubin will go towards the liver to Font size 10, italicized, centered be conjugated and processed. The iron that isreleased from the hemewill be preserved in the storage form of iron in IMPORTANT INFORMATION the body calledFerritin. Bold, Underlined, or Italicized Damaged RBC → Broken down by macrophage → Releasing the heme group ULLET FORMS (STRICTLY FOLLOW; JUST B → Using heme oxygenase they will become ADJUST THE RULER ABOVE) bilirubin → using bilirubin reductase creating unconjugated bilirubin → goes to First Bullet (0.50 on ruler) liver → conjugated bilirubin by UDP ○ Second Bullet (1.25 on ruler) Glucuronyl transferase → gastrointestinal Third Buller (2.00 on ruler) system Fourth Bullet (2.50 on ruler) ○ The probiotics (intestinal flora) in the *thisistoutilizeandmaximizethespaceandfor gastrointestinal system will process the a much cleaner appearance conjugated bilirubin to become STERCOBILINorUROBILINOGEN Stercobilinwill be released through feces Urobilinogenwill be released from the kidneys tourine HEADING SUBHEADING SUB-SUB-SUBHEADING SUB-SUB-SUB-SUBHEADING ONT USED: F Helvetica EXT T 11 and Justified ARGIN M 1.5 cm AGE SETUP P Two Columns (with line in the center) NERI, CAÑEDO, BANTUGAN, ACOSTA, JAINAR, MADJUS |31
